A fundamental problem in neuroscience and medicine is to understand the mechanisms of general anesthesia. This proposal, "Multimodal Functional Imaging of Auditory Perception Under General Anesthesia", is submitted in response to the NINDS program announcement for Mentored Quantitative Research Career Development Awards (K25). The candidate seeks to gain training in the neurobiology and clinical pharmacology of anesthesia in order to apply multimodal functional imaging methods to the study of the mechanisms of general anesthesia. Loss of consciousness under general anesthesia is measured clinically by observing the loss of response to external stimuli. However, auditory perception and memory are possible in patients who are clinically unconscious, which may result in post-operative recall of events during anesthesia. Consequences of post-operative recall include sleep disturbances, dreams, nightmares, flashbacks and anxiety, as well as post-traumatic stress disorder. Clinical anesthetic brain monitors are based on empirical relationships between stereotyped anesthesia-related electroencephalographic (EEG) patterns and clinical assessments of patient awareness, but cannot measure activity within functional brain regions responsible for auditory perception under anesthesia. The goal of this project is to characterize anesthesia-induced changes of function in the auditory system using simultaneous EEG and fMRI. FMRI responses to perception of sound temporal envelope will be measured at varying levels of propofol anesthesia, ranging from light sedation to deep anesthesia, with simultaneous EEG. Changes in auditory perceptual processing measured with fMRI will be related to clinical level of consciousness, propofol drug levels, and anesthesia-related EEG patterns. These studies will provide a means to quantify the amount of perceptual processing that occurs after anesthesia-induced loss of consciousness, as well as the EEG patterns that correlate with loss of perceptual processing. Through this research project, as well as didactic courses and tutorials, the candidate will be trained in the neurobiology and clinical pharmacology of anesthesia. The training provided by this Award will help the candidate achieve the long-term career goal of leading an independent biomedical research program to study the systems neuroscience of anesthesia. General anesthesia is administered to over 50,000 patients daily for medical and surgical procedures, but its basic brain mechanisms are not known. Despite safety improvements, anesthesia results in serious side effects such as cardio-respiratory depression or post-operative recall. Through these studies, we hope to begin developing the fundamental neuroscience knowledge necessary to improve anesthetic drugs and monitoring, and to one day solve the problem of anesthesia-related morbidity.